Amides, C12-18, N-[3-(dimethylamino)propyl]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 September 2009 to 22 October 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-[3-(dimethylamino)propyl] C 12-C18 alkylamide

EC Number:

932-121-8

Cas Number:

1147459-12-8

Molecular formula:

UVCB substance not applicable

IUPAC Name:

N-[3-(dimethylamino)propyl] C 12-C18 alkylamide

Test material form:

solid

Details on test material:

- Name of test material (as cited in study report): Coco amidopropyldimethylamine
- Substance type: Amides, C12-18 (even numbered), N-[3-(dimethylamino)propyl]
- Physical state: Light brown, paste to solid
- Analytical purity: 99.1%
Free dimethyl amino propylamine 0.4%
Free fatty acid 0.5%
- Purity test date: 31 August 2009
- Lot/batch No.: S001824
- Expiration date of the lot/batch: 2nd July 2019
- Storage condition of test material: At room temperature, under nitrogen gas, in a dry and well-ventilated room
- Other: Kept in two transparent glass flasks.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France. Strain Rj: SD (IOPS Han)
- Age at study initiation: 8 or 9 weeks old
- Weight at study initiation: mean 207 ± 14 g
- Fasting period before study: Overnight and up to 4 h after dosing
- Housing: The animals were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm). Each cage contained one to seven animals of the same sex during the acclimation period and one to three rats of the same group during the treatment period. Each cage contained autoclaved sawdust
- Diet (e.g. ad libitum): All the animals had free access to SSNIFF R/M-H pelleted maintenance diet ad libitum, except during the fasting period.
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: From: 10 September 2009 To: 22 October 2009

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Based on the results of the solubility assay.
- Lot/batch no. (if required): 128K0040 and 049K0043
- Purity: Not documented

MAXIMUM DOSE VOLUME APPLIED:
10mL/kg

PREPARATION OF DOSING SOLUTION:
The test item was administered as a solution in the vehicle. The test item was prepared at the chosen concentrations in the vehicle under magnetic stirring for at least 10 minutes. The test item preparation was made freshly on the morning of administration by the CIT Pharmacy and any unused material was discarded that same day.

The dosage form preparations were administered to the animals using a dose volume of 10 mL/kg.
The administration was performed in a single dose by oral route using a metal gavage tube fitted to a 2 mL plastic syringe (0.1 mL graduations).
The volume administered to each animal was adjusted according to body weight determined on the day of treatment.

Doses:

2000, 300 and 50 mg/kg

No. of animals per sex per dose:

Groups of 3 females were used at each dose level. For the 300 and 50 mg/kg levels two groups were dosed in each case

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed frequently during the hours following administration of the test item (day 1), then at least once a day until the end of observation period (day 15). The animals were weighed individually just before administration of the test item on day 1 and then on days 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: No information

Statistics:

No information provided.

Results and discussion

Preliminary study:

Not relevant

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

300 mg/kg bw

Mortality:

At the dose level of 2000 mg/kg, all females were found dead on day 2.
At the dose level of 300 mg/kg, one of the three first treated animals and two of the second treated females were found dead on days 2 and 3.
No mortalities were observed in the 50 mg/kg dose group.

Clinical signs:

other: At the dose level of 2000 mg/kg, hypoactivity or sedation, piloerection, dyspnea (all animals) and soft faeces (one animal) were observed prior to their deaths. In the 300 mg/kg dose group, hypoactivity or sedation, piloerection, dyspnea, hypersalivation

Gross pathology:

In one female in the 2000 mg/kg dose group, soft faeces were observed in the intestines. Macroscopic examination of the main organs of the other animals revealed no apparent abnormalities.

Other findings:

No other observations were noted.

Any other information on results incl. tables

No additional information provided.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions of this study, the dose-level of 300 mg/kg of the test item, Coco amidopropyldimethylamine, could be established as the oral LD50 in rats.

Executive summary:

In a acute oral toxicity study by Acute Toxic Class Method (OECD 423), the test substance, Coco amidopropyldimethylamine was administered in corn oil via oral gavage to female Sprague Dawley rats at dose ranges of 50, 300 and 2000mg/kg. The test substance was administered in a dosage volume of 10mL/kg. One group of 3 females was tested at 2000 mg/kg while at 300 and 50 mg/kg, 2 groups of 3 females each were tested. Clinical signs, mortality and body weight gain were checked for a period of up to 14 days following the single administration of the test item. All animals were subjected to necropsy.

At the dose-level of 2000 mg/kg (three females), all females were found dead on day 2. Hypoactivity or sedation, piloerection, dyspnea and/or soft faeces were observed prior to their deaths. At necropsy, no apparent abnormalities were observed in any animal. At the dose-level of 300 mg/kg (six females), three females were found dead on day 2 or 3. Hypoactivity or sedation, piloerection, dyspnea, hypersalivation, loud breathing and/or tonico-clonic convulsions were noted prior to their deaths. Hypoactivity, piloerection, dyspnea and hypersalivation were observed in three out of six surviving females on day 1. Loud breathing was noted in two out of three surviving females on day 2 then from day 8 until the end of the observation period (day 15) as well as dyspnea and abdominal swelling in one surviving female on days 13 and 15, respectively. A body weight loss was noted in one surviving animal between day 8 and day 15 (-19%). Additionally, when compared to CIT historical control data, a lower body weight gain was noted in one surviving female between day 1 and day 8 (returning to normal thereafter). At necropsy, no apparent abnormalities were observed in any animal. At the dose-level of 50 mg/kg (six females), no mortality or clinical signs were noted during the observation period. When compared to CIT historical control data, a lower body weight gain was noted in two out of six females between day 1 and day 8 (returning to normal thereafter). At necropsy, no apparent abnormalities were observed in any animal.

Under the experimental conditions of this study, the dose-level of 300 mg/kg of the test item, Coco amidopropyldimethylamine, could be established as the oral LD₅₀ in rats.

According to Regulation EC No. 2172/2008, the test substance should be classified as a Category 3 toxicant and should have the signal word Danger and the Hazard Statement H301: Toxic if swallowed. According to Directive 67/548/EEC, the test susbtance should be classified as Harmful and have the symbol Xn and the risk phrase R22: Harmful if swallowed associated with it.